Mycoplasma hominis has been shown to cause human respiratory, urogenital and arthritic diseases. M. hominis strain 1620 was isolated from joint exudates of a patient with septic arthritis. It has several phenotypic properties which differentiate it from the non cytadsorbing, high passage (p. 100+) type strain PG21, including its ability to produce septic arthritis in chimpanzees. Strain 1620 cytadsorbs to human tissue culture substrates and to plastic and glass culture flasks. This cytadsorption is reduced by proteolytic treatment, suggesting that surface protein are involved in attachment. Three monoclonal antibodies (mAbs) were produced that recognize different surface epitopes on a number of proteins, depending on the strain of M. hominis tested. The presence of these epitopes varies from strain to strain without regard to the original tissue source used for isolation. The strain 1620 proteins are all susceptible to surface proteolysis and are hydrophobic in nature and at least some are acylated. Fourteen sequential synovial exudate isolates of M. hominis have been obtained from the same patient over a six-year period. Molecular analysis has shown that protein expression among these strains varies over time. Some co- migrating bands from SDS-PAGE analyses are expressed more in one strain than another and other bands appeared in only a few strains. The proteins recognized by the mAbs raised against strain 1620 also vary. Transient changes among strains at the DNA level were detected using a pMC5 probe of the conserved rRNA operon. These results suggest that surface-exposed proteins may be involved in the attachment and pathogenesis of M. hominis-induced human disease. The antigenic variability of surface proteins on strain 1620 suggests that it may possess a mechanism for altering the protein determinants that it presents to infected host and this would provide a means by which the pathogen may evade the immune defense mechanisms of the host.